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. 2023 Jul 25;24(1):609.
doi: 10.1186/s12891-023-06729-8.

Pyroptosis -related potential diagnostic biomarkers in steroid-induced osteonecrosis of the femoral head

Jin-Lian Chai  1 , Bo-Wen Lu  2 , Hai-Tao Du  3 , Ming-Tao Wen  4 , Xue-Zhen Liang  5   6 , Ping Wang  7   8
Affiliations

Pyroptosis -related potential diagnostic biomarkers in steroid-induced osteonecrosis of the femoral head

Jin-Lian Chai et al. BMC Musculoskelet Disord. .

Abstract

Purpose: Steroid-induced necrosis of the femoral head (SONFH) is a refractory orthopedic hip disease occurring in young and middle-aged people, with glucocorticoids being the most common cause. Previous experimental studies have shown that cell pyroptosis may be involved in the pathological process of SONFH, but its pathogenesis in SONFH is still unclear. This study aims to screen and validate potential pyroptosis-related genes in SONFH diagnosis by bioinformatics analysis to further elucidate the mechanism of pyroptosis in SONFH.

Methods: There were 33 pyroptosis-related genes obtained from the prior reviews. The mRNA expression was downloaded from GSE123568 dataset in the Gene Expression Omnibus (GEO) database, including 10 non-SONFH (following steroid administration) samples and 30 SONFH samples. The pyroptosis-related differentially expressed genes involved in SONFH were identified with "affy" and "limma" R package by intersecting the GSE123568 dataset with pyroptosis genes. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the pyroptosis-related differentially expressed genes involved in SONFH were conducted by "clusterProfiler" R package and visualized by "GOplot" R package. Then, the correlations between the expression levels of the pyroptosis-related differentially expressed genes involved in SONFH were confirmed with "corrplot" R package. Moreover, the protein-protein interaction (PPI) network was analysed by using GeneMANIA database. Next, The ROC curve of pyroptosis-related differentially expressed genes were analyzed by "pROC" R package.

Results: A total of 10 pyroptosis-related differentially expressed genes were identified between the peripheral blood samples of SONFH patients and non-SONFH patients based on the defined criteria, including 20 upregulated genes and 10 downregulated genes. The GO and KEGG pathway enrichment analyses revealed that these 10 pyroptosis-related differentially expressed genes involved in SONFH were particularly enriched in cysteine-type endopeptidase activity involved in apoptotic process, positive regulation of interleukin-1 beta secretion and NOD-like receptor signaling pathway. Correlation analysis revealed significant correlations among the 10 differentially expressed pyroptosis-related genes involved in SONFH. The PPI results demonstrated that the 10 pyroptosis-related differentially expressed genes interacted with each other. Compared to non-SONFH samples, these pyroptosis-related differentially expressed genes had good predictive diagnostic efficacy (AUC = 1.000, CI = 1.000-1.000) in the SONFH samples, and NLRP1 had the highest diagnostic value (AUC: 0.953) in the SONFH samples.

Conclusions: There were 10 potential pyroptosis-related differentially expressed genes involved in SONFH were identified via bioinformatics analysis, which might serve as potential diagnostic biomarkers because they regulated pyroptosis. These results expand the understanding of SONFH associated with pyroptosis and provide new insights to further explore the mechanism of action and diagnosis of pyroptosis associated in SONFH.

Keywords: Bioinformatics analysis; Diagnostic biomarkers; Gene expression omnibus; Pyroptosis; Steroid induced osteonecrosis of the femoral head.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Pyroptosis-related differentially expressed genes in SONFH and non-SONFH samples. A Volcano plot of the pyroptosis-related genes intersected with GSE123568. The red dots represent the significantly up-regulated genes and the blue dots indicate the significantly down-regulated genes. C Circo heatmap of the 10 pyroptosis-related differentially expressed genes in SONFH and non-SONFH samples
Fig. 2
Fig. 2
Bean plot of the 10 differentially expressed pyroptosis -related genes in SONFH and non-SONFH samples
Fig. 3
Fig. 3
GO analysis and KEGG pathway functional enrichment analysis of 10 pyroptosis-related differentially expressed genes in SONFH and non-SONFH samples. A Bar plot of the top 10 enriched BP terms, CC terms MF terms and KEGG pathway terms of these 30 genes. B Circle plot of the top 10 enriched BP terms of these 10 genes. C Circle plot of top 10 enriched KEGG terms of these 10 genes. D Chord plot of relationship among the top 10 enriched BP terms and targets. E Chord plot of relationship among the top 10 enriched KEGG pathway terms and targets. The colours of the nodes range from red to blue in descending order of logFC values. The genes are ordered according to logFC values
Fig. 4
Fig. 4
Spearman correlation analysis of the 10 differentially expressed pyroptosis-related genes in SONFH and non-SONFH samples
Fig. 5
Fig. 5
PPI network of 10 pyroptosis-related differentially expressed genes in SONFH and non-SONFH samples. Black nodes represent target proteins, and connecting colors indicate different correlations. Functional associations between targets were investigated using GeneMANIA. Genes in black circles were query terms while these in gray circle indicate genes associated with query genes
Fig. 6
Fig. 6
ROC curve of the 10 pyroptosis-related differentially expressed genes in SONFH samples
See this image and copyright information in PMC

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